P370: EARLY RESULTS OF A SAFETY AND EFFICACY STUDY OF ALLOGENEIC TRUUCAR™ GC502 IN PATIENTS WITH RELAPSED/REFRACTORY B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA (R/R B-ALL)
Authors: S. Li, Z. Yuan, L. Liu, Y. Li, S. Martina, J. Liu, Z. Li, X. Wang, J. He, W. Zhao, L. Shen, X. Zhang, S. Wang
Journal: HemaSphere (2022)

Background: CD19 targeted autologous CAR-T therapies have been approved for the treatment of r/r B-ALL and greatly improved outcome. However, some patients may not be eligible to receive autologous CAR-T. TruUCAR™ GC502 is an allogeneic, universal CAR-T product with CD19/CD7 dual directed CAR. Preclinical data of GC502 were reported at ASH 2021 (Abstract 148500). Aims: Here, we report early clinical results from a phase I open-label, non-randomized, prospective investigator initiate trial (IIT) of GC502 in r/r B-ALL patients to evaluate safety and preliminary efficacy Methods: GC502 is manufactured using leukopaks from HLA-unmatched healthy donors. It contains a 4-1BB based CD19/CD7 dual directing CAR, a T cell enhancer, and genetically disrupted TRAC and CD7 loci to avoid GvHD and fratricide. Patients (pts) with r/r B-ALL were enrolled and treated with one of two different formulations (A or B) in escalating dose levels ranging from 1.0x107 (DL1) to 1.5x107 (DL2) cells/kg. Prior to infusion of GC502, pts received a Flu/Cy based lymphodepletion regimen. Adverse events, disease response and expansion kinetics were evaluated in this study. Results: At date cut off of Feb. 22, 2022, 4 pts (15-34 yrs) had been enrolled into the investigator initiate study of GC502 (NCT05105867). All of patients were heavily pretreated, and had received either autologous or donor derived CD19 or CD19-CD22 targeted CAR-T in prior lines of therapy. Baseline marrow blast levels ranged from 19.5% to 92% (median 48.1%). 1 pt had extramedullary (EM) involvement. At data cut-off all pts had received a single dose of GC502: 1 pt at DL 1 1.0x107cells/kg in formulation A and 3 patients at DL 2 1.5x107cells/kg – out of which 2 were treated with formulation B. At day 28 post CAR-T infusion, 3 out of 4 response evaluable patients had achieved CR/CRi; 1 pt with EM achieved PR at month 1 and subsequently received allo-HSCT on day 39. TEAEs presented as Gr 3 febrile neutropenia (4/4), Gr 4 thrombocytopenia (1/4) and Gr 3 anemia (3/4). All TEAE resolved after treatment with SOC. Non-hematological TEAE presented as Gr≥3 γ-GT increase (3/4), Gr≤3 AST increase (2/4) and Gr≤3 ALT increase (3/4). 2 pts received formulation A and experienced Gr 3 CRS with a duration of 7 and 10 days respectively (CRS was graded according ASTCT Consensus Grading). CRS presented as Gr 2 in the 2 patients with formulation B with a duration of 9 and 15 days respectively. CRS in all pts was manageable and resolved after treatment with Ruxolitinib, SOC and supportive care. No ICANS or aGvHD were observed. The pt treated in DL 1 did not show adequate GC502 cellular expansion. Peak expansions of GC502 in peripheral blood were observed between week 1-2 in DL 2. Median peak CAR copies were 149,945 copies/ug DNA (range 10,849-195,400). Summary/Conclusion: TruUCAR™ GC502 demonstrated promising early results with a manageable safety profile. Robust CAR-T cell expansion was observed in DL2 at 1.5x107cells/kg in heavily pretreated r/r B-ALL patients, including those previously treated with CD19 or CD19-CD22 CAR-T therapies. The study is ongoing and continues accruing patients.